9L gliosarcoma model

Using rat flank and intracranial 9L gliosarcoma models, Tamargo et al. (70) initially compared the efficacy of polymer and systemically based BCNU. EVAc polymer delivery in the flank model produced significant tumor growth delay relative to systemic administration (15.3 vs. 11.2 days, p < 0.05). In the intracranial model, a 10 mg polymer with 20% (w/w) BCNU polymers dramatically improved survival in animals with established 9L gliosarcoma. EVAc and pCPP SA polymers conferred respective survival advantages of 7.3-fold and 5.4-fold over controls. Systemic BCNU, in contrast, increased survival only 2.4-fold compared to controls. 

A second study in the same established rat intracranial 9L gliosarcoma model evaluated the efficacy of 20% (w/w) BCNU-loaded pCPPrSA polymers vs. direct stereotactic injec-... 

In vitro kinetics studies with 20-40% (w/w) paclitaxel-loaded pCPPrSA (20 80) pol3maers demonstrated sustained drug release approaching 1000 h. Biodistribution studies concordantly revealed tiunorcidal pachtaxel concentrations in the rat brain for > 30 days post-implantation. Median survival in the established rat 9L gliosarcoma model improved from 19.5 days in rats treated with blank polymers to 61.5 days with 20% paclitaxel-loaded pol3rmers (p < 0.001) (105). 

A final study of local paracrine dehvery identified IL-12, a c3rtokine with antiangiogenesis properties in addition to its immimoregulatory effects, as a potential substrate candidate (114). Using the estabhshed rat intracranial 9L gliosarcoma model, the study examined intracranial implantation of IL-12 transduced tumor cells. Reverse transcriptase-poly... 

Efficacy studies in the rat intracranial 9L gliosarcoma model compared systemic and EVAc polymer dexamethasone administration (28). Water weight percentage served as the edema endpoint both intracranial dexamethasone-loaded polymers (79.15% p<0.05) and intraperitoneal dexamethasone injections (79.16% p0.05) were superior to controls (79.45%) and intraperitoneal pol3nner implantation (79.39%). Thus, intracranial pol3nner implantation achieved equivalent edema reduction without the theoretical potential for systemic toxicity. 

R.D. Fross, P.C. Wamke and D.R. Groothuis, Blood flow and blood-to-tissue transport in 9L gliosarcomas the role of the brain tumor model in drug delivery research, J. Neuro-Oncol. 11 (1991) 185-197. 

There are experimental data which show a synergistic or a potentiating effect of chemotherapeutic agents on PDT [80]. The combination of ACNU and HPD-mediated PDT results in significantly increased cytotoxicity in the 9L gliosarcoma [81]. This effect could further be increased by adding hyperthermia as a third treatment modality. The RIF-1 tumor proved to be insensitive to PDT and to doxorubicin but sensitive to cisplatin with no increased cytotoxic effect when both modalities were combined. In the EMT-6 tumor model all three modalities showed a mild effect when used independently, doxorubicin enhanced significantly the effect of PDT, whereas cisplatin did not [82]. Mitomycin C potentiates the effect of PDT in adenocarcinoma [83]. There are no reported clinical data on the interaction of PDT and chemotherapy. 

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